Novel Blood Test Can Find One Cancer Cell Among Millions

A new method for scanning blood samples can detect the spread of cancer at its earliest stages, when only a handful of cancerous cells are present.

Cancer is a problem no matter where it occurs in the body, but it becomes most dangerous when it spreads beyond the original site.

From there, cancer cells break off from the main tumor and circulate in the blood until they lodge elsewhere in the body, spreading the cancer to a new location.

But a new blood test, developed at SRI Biosciences, can detect these cells when they first appear in the bloodstream and detect metastasizing cancer early.

The test, called Fiber-optic Array Scanning Technology, or FASTcell, offers a degree of sensitivity currently unseen in the cancer-detection marketplace.

“What distinguishes FASTcell from other sensors that look for cancer cells is the ability to scan very rapidly,” Lidia Sambucetti, senior director of the Center for Cancer and Metabolism in SRI Biosciences, said. “We can scan 26 million cells in a minute. That allows us to survey all of the blood cells in the sample. This gives us a high sensitivity to find cancer even when there’s only one or two cells present. We can find one single cell in a whole blood sample. We compare it to trying to find a single star in a whole constellation of stars.”

One Cell To Rule Them All

Here's how it works.

First, the patient in question gives a blood sample. Unlike many other cancer tests, FASTcell doesn’t require a biopsy, where a long needle is inserted deep into the patient’s body to grab a small tissue sample from the cancerous area. Biopsies can be painful and must be performed by a specialist.

“What’s nice about this test is that it’s minimally invasive,” Sambucetti said. “We work from a standard blood sample, like might be taken for a standard blood test.”

Next, the scientists remove all the red blood cells from the sample and take the remaining cells—white blood cells,potentially cancerous cells, and others—and spread them out on a glass slide.

“We look for a marker that’s found in the cancer cells and not in the blood cells and tag it with a fluorescent antibody,” Sambucetti said.

The antibody can target specific proteins or sections of DNA that might be found in the cancer cells, called biomarkers. When exposed to a certain kind of light, the antibodies will cause the cells to glow. Then, a laser scanner, developed from laser printing technology, scans the slide and picks out any cells that are glowing. If only a single cell is cancerous, FASTcell can find it.

The More Information, The Better

One of the difficulties of treating cancer is its heterogeneity, meaning that every cancer is different. Cancer forms when a cell’s DNA is damaged and it mutates into an unstable, spreadable form.

For example, two people with pancreatic cancer might not have the same “type” of cancer at all. They probably have different mutations, and their cancer might respond to completely different therapies. This is where FASTcell can help.

“Once we find the cells, then we have the ability to go back to the location of that cell and gather additional information from it using other biomarkers of interest,” Sambucetti said. “We can analyze six biomarkers in each cell that we find. That allows us to, in addition to finding those cells, interrogate each cell for biomarkers that might be important for deciding what type of therapy to use in the patient. It’s useful information for physicians to have about the nature of the disease.”

For example, SRI collaborated with researchers at the City of Hope who were treating breast cancer patients. They examined two biomarkers associated with breast cancer, called HER2 and ER. A cancer-treating drug called Herceptin targets HER2, meaning the drug is only useful if the patient’s cancer shows the correct HER2 mutation. ER, the estrogen receptor, would indicate if the patient’s cancer would respond to hormonal therapy. By testing the cancer cells in the blood for these two receptors, the researchers were able to figure out how best to treat each patient individually based on the specifics of their disease.

Useful After Treatments Are Selected

Not only does this tell doctors which treatments will work, it can also detect which treatments won’t work, sparing patients from expensive treatments that won’t help their cancer and will only make them sicker.

Once the treatments have been selected, FASTcell continues to be useful, Sambucetti said.

“It’s possible to sample patients at any time—before, during, or after therapy,” she explained. “Perhaps during the course of therapy, the cells are undergoing [programmed cell death], which means that they’re responding to the medication. You want to see that in response to a cancer therapy.”

Testing after therapy could also be an early warning system that helps to find out if the patient’s cancer is returning.

In addition to the six biomarkers, FASTcell also provides a clear, crisp picture of each cancerous cell.

“We then image the cells, gathering information about the size and shape of the cell. If the cells are unusual in shape, that’s useful information too,” Sambucetti said. “We still don’t know how to use all this information, but we have the ability to gather a lot of good information from the cells. All that information is very clear because the cells are well-preserved on the glass side.”

Used for Cancer and More

Right now, SRI is using FASTcell to sort for cancerous cells. But collaborating researchers may order custom biomarker sets that can look for any number of cell types, such as cells that have been infected by disease. With some infectious diseases, blood cells can harbor latent viruses, which lurk within cells for weeks or even years before activating and causing the disease to return. FASTcell could find such infections even in a person who was symptom-free.

FASTcell can also detect DNA sequences. For example, it can scan the blood for fetal DNA, which can transfer from fetus to mother during pregnancy. If fetal DNA can be captured, it allows scientists to perform genetic tests on the growing fetus without having to perform an amniocentesis, a testing procedure that carries a risk of miscarriage.

Since FASTcell can be customized for any blood-borne biomarker, its potential applications are vast. Right now, it’s only available for research purposes, but SRI is hoping to begin producing units for sale to clinicians in about two years. Although the machines themselves would be expensive, running them is cheap, and FASTcell can process samples with incredible speed and accuracy to enable personalized medicine.

“What impact it will have on diagnosis is an area that still remains to be understood, but I think it will have a significant benefit once this is more widely available and validated for widespread use,” Sambucetti said.

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